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Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUS
Author(s) -
Preuss KlausDieter,
Held Gerhard,
Kubuschok Boris,
Hung ChunZhu,
Malatsidze Natalia,
Wagner Mathias,
Pfreundschuh Michael
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22686
Subject(s) - paraproteins , antigen , biology , pathogenesis , epitope , immunology , multiple myeloma , antibody , microbiology and biotechnology , monoclonal antibody , monoclonal
Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins have been suggested to play an important role as growth stimulators in the pathogenesis of these neoplasms. To identify such targets, we screened cDNA libraries from human testis, lung and breast cancer, bovine and porcine muscle and wheat germ for reactivity with paraproteins in the sera from 115 patients with MGUS and MM. Of >6 × 10 8 paraprotein–antigen interactions screened, an IgA paraprotein from a female patient bound to sperm‐specific cylicin‐2, and 3 IgG paraproteins bound to tripeptidyl‐peptidase‐II (TPP‐2), insulin‐like growth‐factor binding‐protein‐2 (IGFBP‐2) and porcine kinesin. Specificity was confirmed by reverse Western blots using recombinant antigens. The broad spectrum of auto‐, allo‐ and heteroantigens as targets of human paraproteins in patients without signs of chronic antigenic stimulation renders a causal role of the antigenic stimulus in the pathogenesis of MGUS and MM unlikely. © 2007 Wiley‐Liss, Inc.